This proposal outlines an experimental investigation of the conformational and functional properties for a series of membrane active, synthetic analogues of the cation-carrying antibiotic, valinomycin. The goal of the research is to provide insight into the molecular basis for the biological activity of these compounds and to determine how their structure is related to their ability to bind cations selectively and promote their transport across membranes. In this study the conformations of the free and cation-loaded carrier molecules, together with equilibrium and kinetic constants for carrier-cation interactions will be determined as functions of: (1) the covalent structure of the carriers; (2) the size and charge of the cations; and (3) environmental factors such as solvent polarity and temperature. Nuclear magnetic resonance (NMR) will be the principal method used for these determinations. Studies involve spectral analysis, determination of peptide dihedral angles, location of intramolecular H-bonds, conformational fluctuations, molecular rotation rates and the kinetics of peptide-cation interactions.